American Indians and Alaska Natives (AI/AN) have the highest smoking rates any ethnic group in the United States, at 41% versus 24% for African Americans and Whites. They also have the lowest quit rates of any group, at 8-10% at 6 months. Due to its long cultural significance as a sacred plant, the entirely negative portrayal of tobacco in most smoking cessation programs is inappropriate, leaving programs unsuccessful. In 2003, AI/AN patients from Haskell Health Center requested a culturally-appropriate smoking cessation program, causing the center director to contact the University of Kansas Medical Center Department of Preventive Medicine. Since that time, the larger AI/AN community in Kansas and Missouri has been working collaboratively with KUMC on the development of a culturally-tailored smoking cessation program, as well as several other projects. In 2006, KUMC and several community-based organizations formed the American Indian Health Research and Education Alliance, dedicated to improving the health of AI/AN using community-based participatory research methods. The culturally-tailored smoking cessation program that began the partnership, All Nations Breath of Life (ANBL), has now been developed and pilot tested and is ready for implementation in the urban AI/AN community of the Kansas City Metroplex. Our pilot data are promising; with a 25% quit rate and 80% participant retention at 6-months post-baseline. We will address the following specific aims: (1) To create appropriate infrastructure (personnel, space, supplies, leadership commitment) for the Heart of America Indian Center to serve as the primary site for implementation of ANBL; (2) To examine the acceptability and feasibility of implementing ANBL in an urban AI/AN community; (3) To estimate the effectiveness of ANBL in an urban AI/AN community; and (4) to identify factors that enhance dissemination of ANBL and contribute to program success or failure. We hypothesize that participants in ANBL will quit smoking at a higher rate than currently reported in the literature for the best available programs. In addition, we will conduct a cost-effectiveness analysis of the program to help determine its sustainability. If this project is successful, ANBL can be disseminated to other AI/AN communities to help them quit smoking. By reducing smoking rates in this community, we can ultimately reduce their leading cause of cancer death (lung cancer) and their leading cause of overall death, cardiovascular disease.